The Johns Hopkins University and its partners, Research Institute for Health Sciences [RIHES] and Faculty of Medicine, Chiang Mai University of Public Health Region 10; HIVNET 021 for participating medical centers; Northern Drug Dependence Treatment Center seek to be a Prevention Trial Network (PTN) Unit for Thailand. The purpose of our PTN Unit is to conduct state-of-the-art preventative interventions to slow the acquisition and transmission of HIV infection in this region. We propose to participate in HIV prevention trials in multi-site or single-site investigations in the following areas: (1) To continue our HIVNET sponsored investigation, "Hormonal Contraception and the Risk of HIV Acquisition (HIVNET 021)," which is a consortium of 7 clinical sites in Thailand and a Coordinating Center at RIHES. We are recruiting 2,600 women in 4 regions of Thailand over a 15-month period and following them at 3-month intervals for an average of 24 months with incident HIV and STDs as study endpoints. PTN support for the period June 2000 to July 2002 is requested in this application. (2) To conduct a Phase I safety and acceptability trial of an anorectal microbicidal for men who have sex with men (MSM) in Chiang Mai. Possible products include Nonoxynol-9, other spermicides, BufferGel or other promising compounds, along with promotion of the use of the female condom during anal intercourse. (3) To evaluate the following substance use related interventions: (a) a feasibility study of promoting drug treatment entry among HIV-1 infected drug users who have relapsed to drug use following inpatient drug detoxification at the NDTC in Mae Rim. (4) To conduct a Phase I trial for antenatal/intrapartum prevention of maternal to child transmission (MCT) of HIV-1 infection using ZT monotherapy vs. PETRA (AZT/ETC); PMPA, an investigational new drug that has been demonstrated in the laboratory to have intriguing anti-retroviral effects; a combination of proven anti-retrovirals (e.g. nevirapine and AZT) or other promising compounds, as recommended by the PTN's Perinatal Working Group. Under HIVNET, we received approval for the conduct of a Phase I safety and toxicity study of PMPA in 25 mother/infant pairs in Thailand; due to unexpected complications from the company, we have not yet been able to field this study but anticipate doing so this coming year. Our team has the capacity to rapidly respond to new opportunities in HIV prevention, as might occur within the PTN structure. Our partners have demonstrated over the past 9 years that we have the necessary infrastructure, trained manpower, scientific capability and expertise to both expand our efforts to meet the needs for large population efficacy trials, and to be able to recruit and retain very large, diverse cohorts which might be needed as trials are ready for Phase III implementation.